Influence on Hepatic Ferritin Systems of Tertiary Amine, G-D 131, with Beneficial Effects in Shock.

Abstract

A tertiary amine, N-(2-chloroethyl)-N-(cyclohexylmethyl)-ethylamine hydrochloride (G-D 131), related structurally to the Dibenamine type of adrenergic blocking agent, but altered so that adrenergic blocking properties are lost, shared with Dibenzyline the property of profoundly modifying the ferritin-regulating mechanisms of the liver. In vitro, brief exposure to 10 [mu]g/g of tissue resulted in inhibition of the usual anaerobic release of vasoactive ferritin (VDM) from normal liver slices and in preservation of the aerobic hepatic ferritin-inactivation mechanism despite prolonged anaerobiosis. In vivo, pretreatment of rats with 200 [mu]g of G-D 131/100 g body weight almost doubled the survival rate in drum shock, and administration of 80 [mu]g/100 g (approximately 1/100 of the LD50) resulted in protection against hemorrhagic shock equal to that provided by Dibenzyline which had hitherto proved to be the most effective protective agent. Liver ferritin mechanisms, examined in G-D 131-treated rats following the hemorrhagic procedure, compare favorably with those of normal unshocked rats, releasing no ferritin aerobically and retaining the normal ferritin-inactivation capacity, in contrast to the livers of the control rats which now release ferritin aerobically and are unable to inactivate added ferritin. These observations are regarded as support for the concept that deterioration of the hepatic ferritin mechanisms brings about consequences of major importance for the ability of the animal to survive a standardized shock procedure.